EP1520859B1 - Oligopeptides signaux hydrophiles et leurs procédés d'utilisation à des fins thérapeutiques - Google Patents

Oligopeptides signaux hydrophiles et leurs procédés d'utilisation à des fins thérapeutiques Download PDF

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Publication number
EP1520859B1
EP1520859B1 EP04030374A EP04030374A EP1520859B1 EP 1520859 B1 EP1520859 B1 EP 1520859B1 EP 04030374 A EP04030374 A EP 04030374A EP 04030374 A EP04030374 A EP 04030374A EP 1520859 B1 EP1520859 B1 EP 1520859B1
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EP
European Patent Office
Prior art keywords
sequence
amino acid
prt
topology
artificial
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EP04030374A
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German (de)
English (en)
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EP1520859A2 (fr
EP1520859A3 (fr
EP1520859B9 (fr
Inventor
Matthias Dr. Med. Rath
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Rath Matthias Dr med
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04—Linear peptides containing only normal peptide links
    • C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04—Linear peptides containing only normal peptide links
    • C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids

Definitions

  • the protein code consists of letters words and sentences.
  • the letters (amino acids) and sentences (complete three dimensional protein) had been known before.
  • the new discovery are the protein words or verbs. These protein verbs are represented by signal oligopeptides which are localized on the surface of the protein and are represented by the hydrophyticity maxima of the protein. These signal oligopeptides are enriched in charged amino acids in a versatile arrangement with neutral spacer ammo acids The specific signal character of these oligopeptides is determined by a characteristic combination of conformation and charge within the same signal sequence
  • the discovery of the protein code provides the rationale for deciphering the communication code of diseases. Infectious diseases, cancer, cardiovascular and other diseases develop by means of one or more pathogenicity-mediating proteins. Blocking the signal oligopeptides of these proteins allows the specific therapeutic interception of a pathological communication and thereby blocks disease propagation.
  • Synthetic analogs to signal oligopeptides can be used therapeutically in several ways.
  • synthetic analogues to signal oligopeptides can be used as competitive inhibitors of pathological communication.
  • synthetic analogs to signal oligopeptides can be used as vaccines. This second therapeutic approach makes use of the fact that signal oligopeptides on the surface of the protein are identical with the antigenicity determining epitopes of this protein. Thus, antibodies are interceptors of metabolic communication. By binding to the signal oligopeptide of a protein antibodies and other mediators of immune response reduce or block its metabolic interaction. If synthetic analogs to signal oligopeptides are used as vaccines it is necessary to render these peptides antigenic and to allow their discrimination as 'non-self'. Synthetic analogs to signal oligopeptides can be rendered immunogenic by coupling them to haptens and by other conventional methods.
  • the invention is based on methods by which oligopeptide sequences can be rendered immunogenic.
  • This method is based on the discovery of the primary structural principles determining immunogenicity.
  • the discrimination between self and non-self between species and between individuals is primarily based on amino acid residue substitutions or other residue variations within the signal oligopeptide sequences of a protein.
  • effective therapeutic signal oligopeptide can be rapidly produced in the following way signal oligopeptides of a given protein in one species are the antigenicity determinants of this protein in another species
  • the synthetic signal oligopeptide vaccines are designed by copying corresponding amino acid signal sequences from another species.
  • a glucagon signal oligopeptide vaccine for the treatment of diabetic patients would be based on glucagon signal sequences from rabbits, sheep, mice or other species.
  • a titration of the therapeutic efficiency is possible: The greater the genetic and evolutionary distance of the selected species to humans the greater its antigenicity and consequently the greater its therapeutic efficiency as a vaccine.
  • the protein code is determined by the following principles:
  • a new type of signals is represented by oligopeptides which obtain their characteristic conformation by a specific arrangement of oppositely charged amino acid residues within this oligopeptide sequence. These residues with opposite charge can attract each other thereby modulating a characteristic folding of this signal sequence.
  • RGD the cationic residue arginine and the anionic residue aspartate attract each other leading to a characteristic fording of this tripeptide around the 'spacer' residue glycine.
  • Metabolic disorders A novel therapeutic area for peptide therapy is the treatment of metabolic disorders.
  • the potential of peptide therapy is exemplified here for the treatment of diabetes and hypertension.
  • glucagon the insulin antagonist.
  • the inhibition of glucagon can be accomplished by using the therapeutic peptides analogous to the glucagon signal sequence for direct competitive inhibition or as a vaccine ( Figure 5 ).

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biochemistry (AREA)
  • Toxicology (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Analytical Chemistry (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)

Claims (3)

  1. Oligopeptide consistant en une séquence d'acides aminés Ser-Gln-Asp-Glu-Val-Arg-Glu-Asn telle que représentée dans SEQ ID n° 42 ou Glu-Leu-Ser-Arg-Glu-Ser-Arg-Glu-Gly-Arg telle que représentée dans SEQ ID n° 44.
  2. Composition pharmaceutique comprenant un oligopeptide selon la revendication 1.
  3. Oligopeptide selon la revendication 1 destiné à être utilisé en thérapie.
EP04030374A 1994-01-14 1995-01-12 Oligopeptides signaux hydrophiles et leurs procédés d'utilisation à des fins thérapeutiques Expired - Lifetime EP1520859B9 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US18224894A 1994-01-14 1994-01-14
US182248 1994-01-14
EP95908522A EP0744027B1 (fr) 1994-01-14 1995-01-12 Utilisation des methodes pour identifier des oligopeptides signaux hydrophiles

Related Parent Applications (2)

Application Number Title Priority Date Filing Date
EP95908522A Division EP0744027B1 (fr) 1994-01-14 1995-01-12 Utilisation des methodes pour identifier des oligopeptides signaux hydrophiles
EP95908522.6 Division 1995-07-20

Publications (4)

Publication Number Publication Date
EP1520859A2 EP1520859A2 (fr) 2005-04-06
EP1520859A3 EP1520859A3 (fr) 2008-08-20
EP1520859B1 true EP1520859B1 (fr) 2010-04-14
EP1520859B9 EP1520859B9 (fr) 2010-12-29

Family

ID=22667644

Family Applications (2)

Application Number Title Priority Date Filing Date
EP04030374A Expired - Lifetime EP1520859B9 (fr) 1994-01-14 1995-01-12 Oligopeptides signaux hydrophiles et leurs procédés d'utilisation à des fins thérapeutiques
EP95908522A Expired - Lifetime EP0744027B1 (fr) 1994-01-14 1995-01-12 Utilisation des methodes pour identifier des oligopeptides signaux hydrophiles

Family Applications After (1)

Application Number Title Priority Date Filing Date
EP95908522A Expired - Lifetime EP0744027B1 (fr) 1994-01-14 1995-01-12 Utilisation des methodes pour identifier des oligopeptides signaux hydrophiles

Country Status (8)

Country Link
EP (2) EP1520859B9 (fr)
AT (2) ATE464315T1 (fr)
AU (1) AU1681095A (fr)
DE (2) DE69536065D1 (fr)
DK (1) DK0744027T3 (fr)
ES (2) ES2344643T3 (fr)
PT (1) PT744027E (fr)
WO (1) WO1995019568A1 (fr)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6057294A (en) * 1995-01-16 2000-05-02 Northern Sydney Area Health Service Of Pacific Highway Peptide
GB9615533D0 (en) * 1996-07-24 1996-09-04 Peptide Therapeutics Ltd Diagnostic test for herpes simplex virus type-2
WO1998010792A1 (fr) * 1996-09-11 1998-03-19 Prendergast Patrick T Therapie a but immunitaire
US6902888B1 (en) 1999-05-21 2005-06-07 Myriad Genetics, Inc. Diabetes gene
WO2000071751A1 (fr) * 1999-05-21 2000-11-30 Myriad Genetics, Inc. Gene du diabete
AU2003211501A1 (en) * 2002-02-08 2003-09-02 Nakoshi, Hideo Peptides
WO2009008888A1 (fr) * 2007-07-10 2009-01-15 Matthias Rath Polypeptides issus du virus de la peste porcine africaine utilisés en tant que vaccins et leur utilisation thérapeutique
GB201214493D0 (en) * 2012-08-14 2012-09-26 Univ Ulster Therapies
GB2543550A (en) * 2015-10-21 2017-04-26 Hox Therapeutics Ltd Peptides
CA3066756A1 (fr) 2017-06-15 2018-12-20 Cancer Advances Inc. Compositions et procedes pour induire des immunites humorales et cellulaires contre des tumeurs et un cancer

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4554101A (en) * 1981-01-09 1985-11-19 New York Blood Center, Inc. Identification and preparation of epitopes on antigens and allergens on the basis of hydrophilicity
WO1989005823A1 (fr) * 1987-12-23 1989-06-29 The Upjohn Company Glycoproteines chimeriques contenant des segments immunogeniques des glycoproteines du virus syncytial respiratoire humain
AU611784B2 (en) * 1988-04-22 1991-06-20 Pharmacia & Upjohn Company Chimeric glycoproteins containing immunogenic segments of human parainfluenza virus type 3

Also Published As

Publication number Publication date
AU1681095A (en) 1995-08-01
EP1520859A2 (fr) 2005-04-06
EP0744027A4 (fr) 2000-09-06
WO1995019568A1 (fr) 1995-07-20
EP0744027A1 (fr) 1996-11-27
DK0744027T3 (da) 2005-06-13
DE69536065D1 (de) 2010-05-27
ATE291230T1 (de) 2005-04-15
DE69534077T2 (de) 2005-08-11
EP1520859A3 (fr) 2008-08-20
ES2236703T3 (es) 2005-07-16
DE69534077D1 (de) 2005-04-21
EP1520859B9 (fr) 2010-12-29
EP0744027B1 (fr) 2005-03-16
ATE464315T1 (de) 2010-04-15
PT744027E (pt) 2005-05-31
ES2344643T3 (es) 2010-09-02

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